Tags

Type your tag names separated by a space and hit enter

Retinal ganglion cell dysfunction in mice following acute intraocular pressure is exacerbated by P2X7 receptor knockout.
Sci Rep. 2021 02 18; 11(1):4184.SR

Abstract

There is increasing evidence for the vulnerability of specific retinal ganglion cell (RGC) types in those with glaucoma and in animal models. In addition, the P2X7-receptor (P2X7-R) has been suggested to contribute to RGC death following stimulation and elevated IOP, though its role in RGC dysfunction prior to death has not been examined. Therefore, we examined the effect of an acute, non-ischemic intraocular pressure (IOP) insult (50 mmHg for 30 min) on RGC function in wildtype mice and P2X7-R knockout (P2X7-KO) mice. We examined retinal function using electroretinogram recordings and individual RGC responses using multielectrode arrays, 3 days following acute IOP elevation. Immunohistochemistry was used to examine RGC cell death and P2X7-R expression in several RGC types. Acute intraocular pressure elevation produced pronounced dysfunction in RGCs; whilst other retinal neuronal responses showed lesser changes. Dysfunction at 3 days post-injury was not associated with RGC loss or changes in receptive field size. However, in wildtype animals, OFF-RGCs showed reduced spontaneous and light-elicited activity. In the P2X7-KO, both ON- and OFF-RGC light-elicited responses were reduced. Expression of P2X7-R in wildtype ON-RGC dendrites was higher than in other RGC types. In conclusion, OFF-RGCs were vulnerable to acute IOP elevation and their dysfunction was not rescued by genetic ablation of P2X7-R. Indeed, knockout of P2X7-R also caused ON-RGC dysfunction. These findings aid our understanding of how pressure affects RGC function and suggest treatments targeting the P2X7-R need to be carefully considered.

Authors+Show Affiliations

Department of Anatomy & Neuroscience, University of Melbourne, Melbourne, 3010, Australia.Department of Optometry and Vision Sciences, University of Melbourne, Melbourne, 3010, Australia.Department of Optometry and Vision Sciences, University of Melbourne, Melbourne, 3010, Australia.Department of Optometry and Vision Sciences, University of Melbourne, Melbourne, 3010, Australia.Department of Anatomy & Neuroscience, University of Melbourne, Melbourne, 3010, Australia.Department of Anatomy & Neuroscience, University of Melbourne, Melbourne, 3010, Australia.Department of Anatomy & Neuroscience, University of Melbourne, Melbourne, 3010, Australia. e.fletcher@unimelb.edu.au.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33603067

Citation

Wang, Anna Y M., et al. "Retinal Ganglion Cell Dysfunction in Mice Following Acute Intraocular Pressure Is Exacerbated By P2X7 Receptor Knockout." Scientific Reports, vol. 11, no. 1, 2021, p. 4184.
Wang AYM, Wong VHY, Lee PY, et al. Retinal ganglion cell dysfunction in mice following acute intraocular pressure is exacerbated by P2X7 receptor knockout. Sci Rep. 2021;11(1):4184.
Wang, A. Y. M., Wong, V. H. Y., Lee, P. Y., Bui, B. V., Dudczig, S., Vessey, K. A., & Fletcher, E. L. (2021). Retinal ganglion cell dysfunction in mice following acute intraocular pressure is exacerbated by P2X7 receptor knockout. Scientific Reports, 11(1), 4184. https://doi.org/10.1038/s41598-021-83669-0
Wang AYM, et al. Retinal Ganglion Cell Dysfunction in Mice Following Acute Intraocular Pressure Is Exacerbated By P2X7 Receptor Knockout. Sci Rep. 2021 02 18;11(1):4184. PubMed PMID: 33603067.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Retinal ganglion cell dysfunction in mice following acute intraocular pressure is exacerbated by P2X7 receptor knockout. AU - Wang,Anna Y M, AU - Wong,Vickie H Y, AU - Lee,Pei Ying, AU - Bui,Bang V, AU - Dudczig,Stefanie, AU - Vessey,Kirstan A, AU - Fletcher,Erica L, Y1 - 2021/02/18/ PY - 2020/09/10/received PY - 2020/12/22/accepted PY - 2021/2/19/entrez PY - 2021/2/20/pubmed PY - 2021/2/20/medline SP - 4184 EP - 4184 JF - Scientific reports JO - Sci Rep VL - 11 IS - 1 N2 - There is increasing evidence for the vulnerability of specific retinal ganglion cell (RGC) types in those with glaucoma and in animal models. In addition, the P2X7-receptor (P2X7-R) has been suggested to contribute to RGC death following stimulation and elevated IOP, though its role in RGC dysfunction prior to death has not been examined. Therefore, we examined the effect of an acute, non-ischemic intraocular pressure (IOP) insult (50 mmHg for 30 min) on RGC function in wildtype mice and P2X7-R knockout (P2X7-KO) mice. We examined retinal function using electroretinogram recordings and individual RGC responses using multielectrode arrays, 3 days following acute IOP elevation. Immunohistochemistry was used to examine RGC cell death and P2X7-R expression in several RGC types. Acute intraocular pressure elevation produced pronounced dysfunction in RGCs; whilst other retinal neuronal responses showed lesser changes. Dysfunction at 3 days post-injury was not associated with RGC loss or changes in receptive field size. However, in wildtype animals, OFF-RGCs showed reduced spontaneous and light-elicited activity. In the P2X7-KO, both ON- and OFF-RGC light-elicited responses were reduced. Expression of P2X7-R in wildtype ON-RGC dendrites was higher than in other RGC types. In conclusion, OFF-RGCs were vulnerable to acute IOP elevation and their dysfunction was not rescued by genetic ablation of P2X7-R. Indeed, knockout of P2X7-R also caused ON-RGC dysfunction. These findings aid our understanding of how pressure affects RGC function and suggest treatments targeting the P2X7-R need to be carefully considered. SN - 2045-2322 UR - https://www.unboundmedicine.com/medline/citation/33603067/Retinal_ganglion_cell_dysfunction_in_mice_following_acute_intraocular_pressure_is_exacerbated_by_P2X7_receptor_knockout_ L2 - https://doi.org/10.1038/s41598-021-83669-0 DB - PRIME DP - Unbound Medicine ER -